Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways

Zhang,Yingmei; Xu,Dongbo; Wang,Xiaochun; Lu,Ming; Gao,Bo; Qiao,Xin

doi:10.3892/mmr.2013.1781

Screening of kinase inhibitors targeting BRAF for regulating autophagy based on kinase pathways

Authors:
- Yingmei Zhang
- Dongbo Xu
- Xiaochun Wang
- Ming Lu
- Bo Gao
- Xin Qiao
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Affiliations: Central Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Department of Surgery, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90064, USA
Published online on: November 7, 2013 https://doi.org/10.3892/mmr.2013.1781
Pages: 83-90

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Abstract

The aim of this study was to identify agents that regulate autophagy. A total of 544 differentially expressed genes were screened from the intersection set of GSE2435 and GSE31040, which was obtained from the Gene Expression Omnibus database and 19 differentially expressed kinases were selected according to a 'protein kinase database'. Gene ontology‑biological process (GO-BP) enrichment analysis revealed that the 19 kinases were mainly associated with phosphorylation. The protein-protein interaction network exhibited 30 differentially expressed genes that interacted with BRAF, and GO-BP enrichment analysis showed the function of these genes were mainly involved in cell death and apoptosis. The kinase-kinase inhibitor regulatory network identified16 kinase inhibitors that specifically inhibited BRAF. Previous studies indicated that sorafenib is capable of regulating autophagy and regorafenib has also been reported; however, there have been no studies regarding the regulation of autophagy by afatinib, selumetinib, PD318088, axitinib, TAK-733, GDC-0980, GSK2126458, PLX-4720, AS703026, trametinib, GDC-0941 and PF-04217903. Thus, these kinase inhibitors are potential targets for further study on the regulation of autophagy in the future.

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